Numerous drugs and other substances are known to be nephrotoxic. For example, radiographic contrast media (e.g., “contrast agent” or “dye”), non-steroidal antiinflamatory drugs (NSAID's), amphotericin, cisplatin, methotrexate, acyclovir, gentamicin, acetylcholinesterase inhibitiors, other nephrotoxic drugs, products of tumor lysis and products of rhabdomyolysis are known to cause damage to the kidneys.
In particular, radiologic contrast media (sometimes referred to as contrast agents or dyes) are frequently administered to patients undergoing radiographic investigations, such as fluoroscopy, X-ray, magnetic resonance and ultrasound imaging, to visualize blood vessels or blood flow and/or to enhance the image being obtained. For example, contrast medium may be administered to patients undergoing coronary angiography or other cardiac catheterization procedures. Delivery of the contrast media into a patient's vasculature enables the vasculature of different organs, tissue types, or body compartments to be more clearly observed or identified.
However, the use of radiographic contrast media may be associated with adverse side effects, including nephrotoxicity. In particular, contrast medium-induced nephrotoxicity is known to be an iatrogenic cause of acute renal failure in some patients. It has been reported that use of contrast media is the third most common cause of new onset renal failure in hospital patients. Patients who experience nephrotoxicity may experience changes in serum creatinine, or creatine clearance, at about one to five days after receiving the contrast medium. Consequences may be dramatic and can lead to irreversible renal damage and dialysis.
Acute deterioration in renal function is a recognized complication after coronary angiography, particularly for patients with pre-existing renal insufficiency. For patients with abnormal baseline renal function, the incidence of progressive renal deterioration may be as high as 42%. For hospitalized, critically ill patients, these results carry a poor prognosis for the patient, especially if dialysis becomes necessary. Factors that may predispose a patient for developing acute renal failure include, pre-existing renal insufficiency, diabetes mellitus, cardiovascular disease, including congestive heart failure, aging, and conditions characterized by depletion of effective circulatory volume.
Several mechanisms have been suggested for contrast medium-induced nephropathy. After radiographic contrast medium exposure, a brief period of vasodilation may be followed by renal vasoconstriction leading to intense reduction in renal blood flow, direct toxicity to renal tubular epithelium, tubular obstruction by protein precipitates, complement activation, and renal ischemia. In addition, patients at high risk of developing renal failure, including those with endothelial dysfunction, may not be able to dilate the renal vasculature, and thus experience a prolonged vasoconstrictive response. Vasoconstriction not only causes a decrease in renal blood flow and glomerular filtration rate, but it may also exacerbate medullary ischemia by decreasing oxygen supply since renal oxygen consumption is coupled to renal blood flow.
Attempts to reduce or prevent contrast medium-induced renal failure have included periprocedural hydration, forced diuresis, blood volume expansion, low osmolality versus high osmolality contrast agents, dopamine, calcium channel blockers, mannitol, atrial natriuretic peptide, acetylcholine esterase (ACE) inhibitors, the adenosine antagonist theophylline, endothelin receptor antagonists, and acetylcysteine. The attempts have generally been directed to reduce vasoconstriction and the negative effects that may be associated with vasoconstriction, such as the exacerbation of medullary ischemia. See, Renal Preservation Strategies for High Risk Patients, University of Chicago Prizker School of Medicine, (August 2000).
Mild hypothermia (e.g., approximately 32 degrees Celsius to approximately 36 degrees Celsius) has been shown to reduce metabolic requirements of organs, such as the heart and/or the brain. Indeed, if the hypothermia is systemic, the metabolic demands of the entire body may be reduced, so that the demands placed on the heart may be reduced. Hypothermia may also be effective to reduce ischemia in specific organs and to reduce the potential of organ damage due to such ischemia.
The physiology of hypothermia is fairly well understood. Normal human body temperature (approximately 37 degrees Celsius) may vary by approximately one degree Celsius. As body temperature decreases, resting muscle tone increases to attempt to generate heat, and the peripheral circulation is reduced to decrease blood flow to the skin to attempt to reduce heat loss. Shivering may develop as the body attempts to increase the metabolism and generate heat. When the temperature of the body decreases to approximately 35 degrees Celsius, shivering may be maximal. Below approximately 31 degrees Celsius, oxygen consumption may drop and shivering may cease. Patients with body temperatures below 27 degrees Celsius may be classified as severely hypothermic, and may be characterized by the cessation of voluntary movement, less than half normal cardiac output, and a significant risk of ventricular fibrillation.
One method for inducing hypothermia of a patient is through the use of a heat exchange catheter that is inserted into a blood vessel and used to cool blood flowing through that blood vessel. This method in general is described in U.S. Pat. No. 6,110,168 (Ginsburg), which is expressly incorporated herein by reference. Various heat exchange catheters useable for achieving the endovascular cooling are described in U.S. Pat. No. 5,486,208 (Ginsburg), PCT International Publication WO OO/10494 (Machold et al.), U.S. Pat. No. 6,264,679 (Keller et al.), PCT International Publication WO 01/58397, all of which are expressly incorporated herein by reference.
As indicated above, the potential for shivering is present whenever a patient is cooled below that patient's shivering threshold, which in humans is generally about 35.5° C. When inducing hypothermia below the shivering threshold, it is important to avoid or limit the shivering response in the patient. The avoidance or limiting of the shivering response may be particularly important in patients who suffer from compromised cardiac function and/or metabolic irregularities. An anti-shivering treatment may be administered to prevent or deter shivering. Examples of effective anti-shivering treatments are described in U.S. Pat. No. 6,231,594 (Dae et al.), the content of which is hereby incorporated by reference.
Thus, there remains a need in the art for improving patient outcome and organ preservation in patients that are administered contrast media, including patients who may be predisposed to developing acute renal failure induced by contrast media.